The objective of this proposal is to learn the molecular nature of paired helical filaments (PHF), the main morphological lesion of Alzheimer dementia. Antisera raised against two cycle purified microtubules of normal human brain was reported at light microscopic level binding to structures resembling the neurofibrillary tangles of Alzheimer dementia. Similar results were reported using antiserum raised against a 55K chicken brain protein, suggesting the major structural proteins of PHF are normal constituents. In the following year we will (1) raise antisera to two cycle purified microtubule proteins. Protein bands excised from SDS polyacrylamide gels will also be used as antigens. (2) characterize the antisera and identify the neurofibrillary tangle cross reactive proteins of normal brain by immunoelectrophoresis and by adsorption studies. (3) Utilize the immunoperoxidase method at electron microscopic level to examine whether structures detected by the antiserum are PHF or other subcellular organelles.